Repeated activation of neurotensin receptors sensitizes to the stimulant effect of amphetamine

Rompré, Pierre‐Paul

doi:10.1016/s0014-2999(97)00159-3

Cited by 37 publications

(39 citation statements)

References 16 publications

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“…systemic amphetamine (Elliott and Nemeroff, 1986), multiple intraventricular NT injections sensitized the animals to the locomotor response induced by amphetamine (Rompré, 1997) or cocaine and these effects were suppressed on lesion of the PFC (Blackburn et al, 2004) or systemic administration of a NMDA receptor antagonist . Furthermore, attenuation of cocaine-induced CPP by SR 48692 suggests that this compound counteracted the conditioned responses to cocaine, which was previously suggested to be dependent on NMDA receptors and PFC activation (Tzschentke, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…For instance, activation of NT receptors in this brain area was found to stimulate midbrain dopamine cell firing (Fatigati et al, 2000;Rompré et al, 1998). Moreover, multiple intraventricular NT injections sensitized rats to the locomotor response induced by systemic amphetamine (Rompré, 1997) or cocaine , and these effects were suppressed on lesion of the PFC (Blackburn et al, 2004) or administration of a N-methyl-D-aspartic (NMDA) receptor antagonist .…”

Section: Introductionmentioning

confidence: 99%

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Neurotensin Receptor Antagonist Administered during Cocaine Withdrawal Decreases Locomotor Sensitization and Conditioned Place Preference

Felszeghy

Espinosa

Scarna

et al. 2007

Neuropsychopharmacol

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Chronic use of psychostimulants induces enduringly increased responsiveness to a subsequent psychostimulant injection and sensitivity to drug-associated cues, contributing to drug craving and relapse. Neurotensin (NT), a neuropeptide functionally linked to dopaminergic neurons, was suggested to participate in these phenomena. We and others have reported that SR 48692, an NT receptor antagonist, given in pre-or cotreatments with cocaine or amphetamine, alters some behavioral effects of these drugs in rats. However, its efficacy when applied following repeated cocaine administration remains unknown. We, therefore, evaluated the ability of SR 48692, administered after a cocaine regimen, to interfere with the expression of locomotor sensitization and conditioned place preference (CPP) in rats. We demonstrated that the expression of locomotor sensitization, induced by four cocaine injections (15 mg/kg, i.p.) every other day and a cocaine challenge 1 week later, was attenuated by a subsequent 2-week daily administration of SR 48692 (1 mg/kg, i.p.). Furthermore, the expression of cocaine-induced CPP was suppressed by a 10-day SR 48692 treatment started after the conditioning period (four 15 mg/kg cocaine injections every other day). Taken together, our data show that a chronic SR 48692 treatment given after a cocaine regimen partly reverses the expression of locomotor sensitization and CPP in the rat, suggesting that NT participates in the maintenance of these behaviors. Our results support the hypothesis that targeting neuromodulatory systems, such as the NT systems may offer new strategies in the treatment of drug addiction.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurotensin Receptor Antagonist Administered during Cocaine Withdrawal Decreases Locomotor Sensitization and Conditioned Place Preference

Felszeghy

Espinosa

Scarna

et al. 2007

Neuropsychopharmacol

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“…Dopaminergic neurons release dopamine not only from axon terminals, but also in somatodendritic areas in the midbrain (Geffen et al, 1976;Kalivas et al, 1989). Locally released dopamine can bind to D 2 type autoreceptors to inhibit dopamine neuron impulse activity through activation of G-protein-coupled potassium (GIRK) channels (Lacey et al, 1987;Pucak and Grace, 1994;Beckstead et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…NT modulates dopaminergic function, and dysregulation of NT signaling is associated with dopaminergic pathologies (Boules et al, 2013). Elevated levels of NT in the midbrain promote motivated behavior, and NT receptor activation in the ventral tegmental area (VTA) is required to induce behavioral sensitization to amphetamine (Panayi et al, 2005;Kempadoo et al, 2013). Although NT can produce longlasting effects on behavior (Rompré, 1997) the cellular mechanisms responsible for these effects are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Neurotensin Induces Presynaptic Depression of D2 Dopamine Autoreceptor-Mediated Neurotransmission in Midbrain Dopaminergic Neurons

Piccart

Courtney

Branch

et al. 2015

Journal of Neuroscience

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Increased dopaminergic signaling is a hallmark of severe mesencephalic pathologies such as schizophrenia and psychostimulant abuse. Activity of midbrain dopaminergic neurons is under strict control of inhibitory D 2 autoreceptors. Application of the modulatory peptide neurotensin (NT) to midbrain dopaminergic neurons transiently increases activity by decreasing D 2 dopamine autoreceptor function, yet little is known about the mechanisms that underlie long-lasting effects. Here, we performed patch-clamp electrophysiology and fast-scan cyclic voltammetry in mouse brain slices to determine the effects of NT on dopamine autoreceptor-mediated neurotransmission. Application of the active peptide fragment NT 8 -13 produced synaptic depression that exhibited short-and long-term components. Sustained depression of D 2 autoreceptor signaling required activation of the type 2 NT receptor and the protein phosphatase calcineurin. NT application increased paired-pulse ratios and decreased extracellular levels of somatodendritic dopamine, consistent with a decrease in presynaptic dopamine release. Surprisingly, we observed that electrically induced long-term depression of dopaminergic neurotransmission that we reported previously was also dependent on type 2 NT receptors and calcineurin. Because electrically induced depression, but not NT-induced depression, was blocked by postsynaptic calcium chelation, our findings suggest that endogenous NT may act through a local circuit to decrease presynaptic dopamine release. The current research provides a mechanism through which augmented NT release can produce a long-lasting increase in membrane excitability of midbrain dopamine neurons.

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“…Finally, cross-sensitization between NT and psychostimulants has been observed. Indeed, repeated activation of NT receptors in rats sensitizes to the stimulant effect of amphetamine (Rompré 1997) and reciprocally, rats which develop enhanced locomotor response to the specific DA uptake inhibitor GBR 12783 are also sensitized to the stimulant motor effect of ] NT, a NT agonist (Boulay et al 1996).…”

mentioning

confidence: 99%

Chronic Blockade of Neurotensin Receptors Strongly Reduces Sensitized, but Not Acute, Behavioral Response to D-amphetamine

Panayi

Dorso

Lambás‐Señas

et al. 2002

Neuropsychopharmacology

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This study investigated the effect of a chronic blockade of neurotensin (NT) receptors on the sensitized behavioral response to amphetamine using a nonpeptide NT receptor antagonist, SR 48692. Rats received four injections of D-amphetamine (0.5 or 1 mg/kg, IP) every other day (day 1, 3, 5 and 7) and were then challenged with the same dose of amphetamine after a 6-day withdrawal (day 14) to establish the presence of locomotor sensitization. Daily administration of SR 48692 (1 mg/kg, IP) throughout the amphetamine regimen (day 1 to day 14) almost completely blocked the sensitized locomotor response to amphetamine without affecting stereotyped behaviors (experiment 1). The decreased amphetamine-induced sensitization in chronically SR 48692-treated rats did not appear to result from an influence on basal locomotor activity, as chronic SR 48692 treatment did not modify the spontaneous locomotor activity developed in response to mild stresses (experiment 2). Moreover, we showed that chronic pretreatment with SR 48692 (1 mg/kg, 14 daily IP injections) had no effect on the locomotor activation induced by a single IP administration of amphetamine (experiment 3). These data suggest that a sustained blockade of NTRepeated intermittent administration of psychostimulants, such as amphetamine and cocaine, leads to a progressive enhancement of their behavioral stimulant effects, as well as a long-lasting hyperreactivity in response to environmental or pharmacological challenges (Antelman et al. 1980;Kalivas and Stewart 1991). This phenomenon, termed behavioral sensitization, is considered as a useful animal model for drug-induced psychosis and drug craving in humans (Robinson and Becker 1986;Robinson and Berridge 1993;Lieberman et al. 1997;Laruelle 2000).The mesoaccumbens dopaminergic (DA) system, which originates within the ventral tegmental area (VTA) and projects to the nucleus accumbens (NAC), plays an important role in the behavioral sensitization to psychostimulants. Thus, repeated injections of am- phetamine into the VTA produce sensitized locomotor responses to systemic injections of amphetamine, cocaine and morphine. In contrast, although amphetamine produces locomotor stimulation upon acute injection into the NAC, repeated intra-NAC injections do not lead to sensitization (Kalivas and Weber 1988;Vezina and Stewart 1990; Hooks et al. 1992; Cador et al. 1995). Other studies have established that the mechanisms leading to the induction of sensitization require the action of DA, somatodendritically released by amphetamine, on D1 receptors in the VTA whereas DA release in the NAC appears as the prime event for the expression of behavioral sensitization (Vezina 1993(Vezina , 1996Pierce and Kalivas 1997a). However, recent studies support the view that the neural underpinnings of behavioral sensitization implicate additional limbic areas and neurotransmitters such as the medial prefrontal cortex (mPFC) and its glutamatergic components (Wolf 1998; Cador et al. 1999) or the ventral pallidum and its GABAergic components (Pier...

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Repeated activation of neurotensin receptors sensitizes to the stimulant effect of amphetamine

Cited by 37 publications

References 16 publications

Neurotensin Receptor Antagonist Administered during Cocaine Withdrawal Decreases Locomotor Sensitization and Conditioned Place Preference

Neurotensin Receptor Antagonist Administered during Cocaine Withdrawal Decreases Locomotor Sensitization and Conditioned Place Preference

Neurotensin Induces Presynaptic Depression of D2 Dopamine Autoreceptor-Mediated Neurotransmission in Midbrain Dopaminergic Neurons

Chronic Blockade of Neurotensin Receptors Strongly Reduces Sensitized, but Not Acute, Behavioral Response to D-amphetamine

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